This invention relates to 1-carba(dethia)cephalosporin antibiotics, intermediates for the preparation thereof, to pharmaceutical formulations comprising the antibiotics, and to a method for the treatment of infectious diseases in man and animals.
The 1-carba(dethia)cephalosporin antibiotics have the bicyclic ring system represented by the following formula wherein the numbering system is that commonly employed in the arbitrary cepham nomenclature system. ##STR3## The 1-carba(1-dethia)cephalosporins are referred to herein for convenience as 1-carbacephalosporins or as 1-carba-3-cephem-4-carboxylic acids or numbered derivatives thereof. Alternatively, the compounds are 3,7disubstituted derivatives of 2-carboxy-8-oxo-1-azabicyclo[4.2.0]oct-2-enes.
The preparation of 1-carbacephalosporins and C-3 substituted methyl derivatives thereof is taught broadly by Christensen et al., in U.S. Pat. No. 4,226,866. Hirata et al., in U.K. patent application No. 2041923, teach a method for preparing 3-H and 3-halo 1-carbacephalosporins, while Hatanaka et al., Tetrahedron Letters, 24, No. 44, pp. 4837-4838 (1983), teach a method for preparing a 3-hydroxy-(.+-.)-1-carbacephalosporin. A variety of 3-hydroxy-1-carbacephalosporins are also provided in EPO Patent Application Publication 209,352 while their 3-triflate (3-trifluoromethanesulfonic acid) esters are disclosed in EPO Patent Application Publication 211,540.
Although many safe and potent antibiotics of the .beta.-lactam class are known and used clinically, the research into this class continues in an effort to find antibiotics with improved efficacy, particularly against microorganisms insensitive or resistant to the known antibiotics.